Microsphere infusion reverses vasoconstrictor‐mediated change in hindlimb oxygen uptake and energy status

Abstract

The vasoconstrictors, angiotensin II (AII) and serotonin (5-HT) produce opposing metabolic effects and appear to control different flow routes in the constant-flow perfused rat hindlimb. In the present study the association between vascular flow route recruitment and metabolism was assessed by selective microsphere embolism of either route. Microspheres (MS, 11.9 +/- 0.1 microns, mean +/- SE diameter) were injected during AII, 5-HT or vehicle infusions (basal conditions) and the effects on hindlimb (4.7 +/- 0.1 g muscle) oxygen uptake (VO2) and indices of energy status CrP/Cr, CrP/ATP and energy charge (EC) of the calf muscle group assessed. MS (1.5 x 10(6)) injected during vehicle, or 5-HT infusion increased VO2 (P < 0.05) but did not affect energy status. During AII, MS decreased VO2. Change in VO2 correlated positively with CrP/Cr (r = 0.68, P < 0.0001) and CrP/ATP (r = 0.51, P < 0.001) but not EC (r = 0.08, P = 0.59). MS (1.5 x 10(6)) increased pressure but did not affect the flow rate. The metabolic changes resulting from 1.5 x 10(6) microspheres were intensified by a second injection of 1.5 x 10(6) microspheres but further injection (> 3.0 x 10(6) microspheres) began to inhibit flow. It is concluded that a finite number (< or = 3.0 x 10(6)) of microspheres of 11.9 microns diameter has opposite effects on VO2 depending on the vasoconstrictor present and that these effects result from the occlusion of the different vascular route accessed by each vasoconstrictor. The data support the proposal that hindlimb metabolism can be controlled by vasoconstrictors as a result of selective vascular recruitment.

Graded occlusion of perfused rat muscle vasculature decreases insulin action

“…It is important to note that there are similarities in the effect on muscle metabolism after introduction of the MS (particularly 30 × 10 6 MS) to what has been observed previously when 5-HT was infused [31]. In both situations, when the muscle has been freeze-clamped and assayed, the EC remained unaffected, but the PCr/Cr ratio was decreased by approx.…”

“…Thus the inhibitory effect of 5-HT on hindlimb muscle metabolism was partly reversed by injection of MS [31], even though the perfusion pressure increased further. Thus we concluded that, if 5-HT had acted to vasoconstrict entry to the nutritive route and redirect flow to the non-nutritive route, the addition of MS lodged in the non-nutritive route redirected flow back to the nutritive route and, hence, the partial recovery of metabolism.…”

“…From a previous study [31], we concluded that MS of 15 µm in diameter can either block the nutritive or non-nutritive route depending on the predominant flow distribution at the time of injection of the MS. We noted that MS can reverse a metabolic effect that a vasoconstrictor has imposed on muscle metabolism by rediverting flow back to its original (pre-vasoconstrictor) pattern. Thus the inhibitory effect of 5-HT on hindlimb muscle metabolism was partly reversed by injection of MS [31], even though the perfusion pressure increased further.…”

Blood flow and muscle metabolism: a focus on insulin action

“…As indicated above, the constant vasomotion activity may allow the sharing of this over the entire muscle with time. Evidence to date shows that only the phosphocreatine-to-creatine ratio is compromised by a low ratio of nutritive to nonnutritive flow, and this is reversed when the nutritive-to-nonnutritive ratio is increased (187). For present considerations, the presence of this nonnutritive route in muscle may explain two phenomena that are developed further in sections below.…”

Vascular Occlusion in a Porcine Flap Model: Effects on Blood Cell Concentration and Oxygenation

“…This is believed to be partly the result of an altered perfusion pattern, through an increase in arteriovenous shunting away from the affected capillary bed. 20 , 21 Also, it can be speculated that the oxygen extraction capacity of the tissue is reduced as a result of its congested state and that the metabolic activity of the congested tissue is downregulated by the increased release of vasoactive substances, including adenosine, 22 and serotonin 23 as well as a decreased release of nitric oxide. 24 Similar results have been reported in experimental models of vascular trauma, in which an uncoupling was suggested between tissue metabolism and altered microvascular blood flow.…”